Biomedical subjects
Publications and source records attributed to A N Stukov.
Acoustic resonance induced by theta-rhythm modulation of bioelectric activity caused moderate inhibition of solid Ehrlich tumors to take place and extended murine life span. No untoward side-effects were registered.
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Toxicity and antitumor action of two new complex compounds of rhenium (K2 [ReCl6] and [ReCl(4).2C6H4N2]) were investigated. LD50 of K2 [ReCl6], i.v., was 136 +/- 37 mg/kg; i.p.,--272 +/- 74 mg/kg. LD50 of [ReCl(4).2C6H4N2], i.v., was 543 +/- 148 mg/kg; i.p., 600 mg/kg was tolerable. Single maximum tolerable dose of 200 mg/kg K2 [ReCl6], i.p., did not influence the growth of ascitic tumor of Ehrlich, nor did daily intravenous dose of 50 mg/kg inhibit solid tumor of Ehrlich. No inhibition by [ReCl(4).2C6H4N2] was registered when 25 or 50 mg/kg were administered.
An additional criterion is suggested for description of effectiveness of therapy of experimental tumors--tumor growth index. It is a ratio of area covered by the kinetic curve of tumor growth in the study group and that in control. The index is intended to describe the efficacy of therapy in terms of degree and duration of the effect.
The results of an all-round examination and complex treatment of 323 patients with renal cell carcinoma were evaluated. Locally advanced tumors were diagnosed in 143 (44.3%) and extended ones--in 180 (66.7%). In patients with locally advanced tumor who had undergone nephrectomy after embolization or chemoembolization, 12-, 24- and 36-month survival rates showed no significant difference. In patients with extended renal carcinoma, 2- and 3-year survival was significantly higher after chemoembolization than after standard embolization of the renal artery.
An evaluation of the treatment of 42 patients with extended primary hepatic tumors and multiple intrahepatic metastases of colorectal carcinoma established the effectiveness of a newly-developed fat-soluble cytostatic drug--dioxadet, used for chemoembolization particularly, when foci fed from small arterial vessels were located along the periphery.
1,3-dioxan- and 1,3-propane diol derivatives of alkyl nitrosourea have been synthesized and studied. Like other 2/chloroethylnitrosoureas, they exerted pronounced influence on a wide range of transplantable tumors, including those transplanted intracranially. Antitumor effect was found to depend on C5 and C2 atom substituent in the 1,3-dioxan cycle and 1,3-propane diol, respectively. The therapeutic effect and toxicity of 1,3-propane diol derivatives were higher than those of 1,3-dioxan. The substances lost all antitumor properties if a methyl group was substituted for the 2-chloroethyl one, even though a nitroso group was retained in their structure.
In experiments using mice and rats with transplantable Ehrlich ascites tumors, sarcoma-180 and adenocarcinoma of Walker, antitumor activity of doxorubicin in combination with disodium salt of 1,1-methylenediphosphonic acid proved higher than that of doxorubicin alone. Most advantage was gained with daily treatment. The toxic effect of said complex treatment seemed to differ slightly from that of doxorubicin as judged on the basis of survival, changes in body mass and peripheral blood count.
A stage II of the joint clinical study of Dioxadet, an ethylene imine drug, was carried out to evaluate its therapeutic effect in 229 patients and side-effects in 239 patients with malignancies of various sites. Marked therapeutic effect was observed in ascitic malignancies of the ovary and a moderate one--in disseminated breast cancer. The most frequent side-effect was reversible myelodepression, often delayed.
The study was concerned with a relationship between a decrease in NAD concentration and inhibition of precursor utilization for NAD biosynthesis, on the one hand, and inhibition of Ehrlich ascitic carcinoma growth in response to treatment with embichin, cyclophosphamide, thiophosphamide, adriablastin and methotrexate, on the other. The antitumor effect of drugs was found to be determined by degree of inhibition of precursor utilization for NAD biosynthesis but not by a decrease in NAD level. A relationship between alteration of synchronous induction of NAD and poly (ADP-ribose) biosynthesis rates and reversibility of the antitumor effect of drugs is discussed.
It was found that repeated transplantation of ACATOL strain cells resulted in a loss of their sensitivity to growth-stimulating effect of pentagastrin. The effect of gastrin receptor antagonist proglumide, on ACATOL cells growth was inconstant. ACATOL tumor was sensitive to VIP and glucagon in vitro (as shown by adenylate cyclase activity assay), that makes the model promising for selecting potent hormone drugs against colorectal cancer.
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A newly-developed antitumor drug Dioxadet is capable of passing the blood-brain barrier. The specific activity of rat brain tissue ranged 8-55% of that of blood at different periods after intraperitoneal injection of 14C-labelled Dioxadet. Dioxadet treatment of mice and rats bearing intracranially-transplanted L1210 leukemia and glioma 35 was followed by a 38-48 and 29% increase in survival, respectively.
The paper discusses the biological properties of 2-(2-furyl)-5-oxymethyl-5-(2,4-diethyleneimino-1,3,5-triazine- 6-yl) amino-1,3-dioxane (furizil), synthesized by substituting ethyleneimine groups for chlorine atoms in individual stereoisomer of a dichlorotriazine derivative. Furizil was found to inhibit the growth of Ehrlich's tumor, Walker's carcinosarcoma, sarcoma 45 and rat ovarian tumors, the inhibition rate ranging 76-100%. Parenterally administered, LD50 appeared to be 6 mg/kg for rats and 15 mg/kg for mice. Studies of chronic toxicity established damaging effects of furizil on hematopoietic, gastrointestinal and reproductive organs. Toxic effects subsided 1-2 weeks after the drug withdrawal.
Zajdela's ascites hepatoma of rats was treated with diverse combinations of 5-fluorouracil (5-FU) and cyclophosphane to study antitumour effect and the intensity of inhibiting the synthesis of nucleic acids. It was established that administration of 5-FU during the first three days and CP during the next three days in doses producing no effect when the drugs are given alone leads to an abrupt inhibition of tumour growth with concurrent inhibition of the synthesis of DNA and all fractions of total RNA. Administration of the drugs in the same succession but in higher doses that produce an inhibition of tumour growth (when the drugs are given alone) results in an antitumour action without eliciting pronounced side effect on bone marrow hemopoiesis.
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A new Soviet preparation for colour lymphography--chromolymphotrast--is presented in this paper. Radiopaque lymphography with the use of chromolymphotrast was carried out upon more than 50 patients with carcinoma of the uterine cervix and of the body of the womb. Besides, there is information concerning a successful use of the chromolymphotrast in cases of cancer of the vulva, mammary gland and rectum. Colour lymphography with the use of chromolymphotrast contributes to a more complete removal of lymphatic collectors. After a preliminary lymphography surgical interventions have acquired a radical character in 93.6% of operations on lymphatic nodes, thus adding to a decrease of the incidence rate of regional recurrences. The national medical industry has proceeded to the production of the preparation, which builds up the conditions for a broad use of colour radiopaque lymphography in oncology.